Safety Study of Oral Azacitidine (CC-486) as Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS).

• Status: Completed
• Trial end date: 2017-05-26
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to determine the maximal tolerated dose and schedule of CC-486, known as oral azacitidine, in patients with AML or MDS after allogeneic hematopoetic stem cell transplant (HSCT). HSCT is more frequently used in AML or MDS as a potential curative therapy. However, disease recurrence/relapse and graft-versus-host disease (GVHD) remain the principal causes of fatal complications after transplantation. Oral azacitidine has significant activity in MDS and AML. Oral azacitidine has also demonstrated immunomodulatory activity in AML patients after allogeneic HSCT. An oral formulation of oral azacitidine provides a convenient route of administration and an opportunity to deliver the drug over a prolonged schedule.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celgene; Celgene Corporation
• Treatments: Azacitidine; Cc-486

Criteria

Inclusion Criteria:

• Histologically confirmed Myelodysplastic Syndromes or Acute Myeloid Leukemia undergoing allogeneic hematopoietic stem cell transplantation with either peripheral blood or bone marrow as the source of hematopoietic stem cells

At the time of allogeneic HSCT:

• No prior allogeneic HSCT; and

• No more than 1 antigen mismatch at Human Leukocyte Antigen (HLA)-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor; and

• Bone marrow blast < 20% if MDS or ≤ 10% if AML; and

• Peripheral blood blast ≤ 5%

Be able to start study drug between 42 to 84 days following allogeneic HSCT

Post transplant bone marrow blast count ≤ 5% confirmed within 21 days prior to starting study therapy

Adequate engraftment within 14 days prior to starting study therapy:

• Absolute Neutrophil count (ANC) ≥ 1.0 x 10^9/L without daily use of myeloid growth factor; and

• Platelet count 75 x 10^9/L without platelet transfusion within one week.

Adequate organ function:

• Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN)

• Serum bilirubin < 2 x ULN

• Serum creatinine < 2 x ULN

Adequate coagulation (Prothrombin time [PT] ≤ 15 seconds, Partial thromboplastin time (PTT) ≤ 40 seconds, and/or International normalized ratio [INR] ≤ 1.5)

Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL at screening).

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Must agree to follow protocol-specified pregnancy precautions

Exclusion Criteria:

• Use of any of the following after transplantation and prior to starting oral azacitidine:

• Chemotherapeutic agents for chemotherapy

• Investigational agents/therapies

• Azacitidine, decitabine or other demethylating agents

• Lenalidomide, thalidomide and pomalidomide

Active Graft-versus-host disease (GVHD) grade II or higher

Any evidence of gastrointestinal (GI) GVHD

Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg

Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)

Active uncontrolled systemic fungal, bacterial or viral infection

Presence of malignancies, other than MDS or AML, within the previous 12 months

Significant active cardiac disease within the previous 6 months